Department of Otorhinolaryngology Head and Neck Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Department of Otorhinolaryngology Head and Neck Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China,
Int Arch Allergy Immunol. 2021;182(3):210-219. doi: 10.1159/000509403. Epub 2021 Jan 21.
This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR).
Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR).
The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs.
The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.
本研究旨在探讨 microRNA-96-5p（miR-96-5p）在变应性鼻炎（AR）病理生理过程中的调节作用。
收集 AR 患者和健康对照者的鼻黏膜组织样本。用人白细胞介素（IL）-13 刺激人鼻上皮细胞（HNECs）建立体外 AR 模型。通过 qPCR、Western blot 或 ELISA 测量靶基因和蛋白的表达。通过双荧光素酶报告基因检测和 pull-down 实验证实 miR-96-5p 与 DEP 结构域含有哺乳动物雷帕霉素靶蛋白相互作用蛋白（DEPTOR）之间的相互作用。
AR 患者 miR-96-5p 水平升高，DEPTOR 表达降低。IL-13 刺激后，HNECs 中促炎细胞因子表达明显增加，哺乳动物雷帕霉素（mTOR）/NF-κB 通路被激活。miR-96-5p 下调减轻了 IL-13 的刺激作用。DEPTOR 是 miR-96-5p 的靶基因。DEPTOR 敲低逆转了 miR-96-5p 抑制剂对 IL-13 刺激的 HNECs 的作用。
本研究表明，miR-96-5p 和 DEPTOR 在 AR 鼻黏膜中异常表达。miR-96-5p 下调通过靶向 DEPTOR 抑制炎症细胞因子的产生和 mTOR/NF-κB 通路的激活。这些发现表明，miR-96-5p 可作为 AR 诊断标志物和治疗靶点。
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